Tailored endothelialization enabled by engineered endothelial cell vesicles accelerates remodeling of small-diameter vascular grafts.

Current gold standard for the replacement of small-diameter blood vessel (ID < 4 mm) is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts (SDVG) on weak endothelialization, intimal hyperplasia and low patency. Herein, we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling. The engineered endothelial cell vesicles were modified with azide groups (ECVs-N3) through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry, and thus fabricating ECVG (ECVs-N3 modified SDVG), which assists inhibition of platelet adhesion and activation, promotion of ECs adhesion and enhancement of anti-inflammation. Furthermore, In vivo single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL, and the tailored endothelialization enabled to convert endothelial cells (ECs) into some specific ECs clusters. One of the specific cluster, Endo_C5 cluster, was only detected in ECVG. Consequently, our study integrates the engineered membrane vesicles of ECVs-N3 from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells, and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.

Topological Rearrangement-Induced Mesoscale Phase Redistribution to Enhance the Fatigue Resistance of Polymer Blends.

Maintaining a high modulus to simultaneously withstand deformation and increase fatigue resistance to restrict crack propagation in a material presents a significant challenge. In this work, a straightforward strategy was developed to address this issue in polymers. A dynamic network was incorporated into a permanent one prior to the formation of the latter, and two incompatible polymer networks were created to prevent common phase separation. The mechanical and fatigue resistance properties were substantially enhanced by the exact modulation of the soft and hard phase distribution by precise control over the densities of dynamic and permanent networks as well as the number of reprocessing steps. The experimental results demonstrated a nearly 9-fold increase in the fatigue life of polyurethane compared with traditional design methods and a 2.5 times increase in modulus. This strategy shows potential for the design of fatigue-resistant thermosetting and thermoplastic materials. The results offer new insight into the development of durable, high-performance materials that are reprocessable and compatible.

Quantitative identification on spatial mismatch characteristics between supply and demand of carbon sequestration services.

Exploring the mismatch between supply and demand (SD) for carbon sequestration services (CSS) is essential for achieving the "double carbon" goal. However, more studies are needed on the traits of the spatial mismatch between SD in mountainous cities. We used the CASA model and the IPCC emission factor approach to address this issue and quantify the SD of CSS in Chongqing. Second, we established a matching relationship model for the SD of CSS in Chongqing. Finally, we applied the Structural Equation Model with the Partial Dependence Plots model to reveal the influencing factors and internal mechanisms of spatial mismatch between the SD of CSS in Chongqing. The outcomes confirmed a decrease in fashion in the total supply of CSS in Chongqing and growth in fashion in general demand from 2000 to 2020. The SD mismatch was mainly concentrated inside the central city and other built-up areas. The SD mismatch area had increased by 390%, indicating a continuous upward trend. In exploring the factors influencing the mismatch between the SD of CSS in Chongqing, supply is mainly positively influenced by NDVI, and demand and supply-demand relationships are influenced by population density and LUCC. We proposed policy suggestions to alleviate the spatial mismatch and practical significance for achieving the "double carbon" goal and promoting sustainable development.

Generating open-source 3D phytoplankton models by integrating photogrammetry with scanning electron microscopy.

The community structure and ecological function of marine ecosystems are critically dependent on phytoplankton. However, our understanding of phytoplankton is limited due to the lack of detailed information on their morphology. To address this gap, we developed a framework that combines scanning electron microscopy (SEM) with photogrammetry to create realistic 3D (three-dimensional) models of phytoplankton. The workflow of this framework is demonstrated using two marine algal species, one dinoflagellate Prorocentrum micans and one diatom Halamphora sp. The resulting 3D models are made openly available and allow users to interact with phytoplankton and their complex structures virtually (digitally) and tangibly (3D printing). They also allow for surface area and biovolume calculations of phytoplankton, as well as the exploration of their light scattering properties, which are both important for ecosystem modeling. Additionally, by presenting these models to the public, it bridges the gap between scientific inquiry and education, promoting broader awareness on the importance of phytoplankton.

Jianwei Xiaoyan granule ameliorates chronic atrophic gastritis by regulating HIF-1α-VEGF pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. PURPOSE: To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. METHODS: In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. RESULTS: Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin, paeoniflorin, lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability, migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 µg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot, immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. CONCLUSION: JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.

A 62.2dB SNDR Event-Driven Level-Crossing ADC with SAR-Assisted Delay Compensation Loop for Time-Sparse Biomedical Signal Acquisition.

This paper proposed an event-driven clockless level-crossing ADC (LC-ADC) suitable for biomedical applications. Thanks to the LC loop, the sampling rate of the converter automatically adapts to the input activities. Activity-dependent power consumption and data compression can thus be realized, saving system power, especially during time-sparse signal acquisition. Meanwhile, a SAR-assisted loop is exploited to resolve the loop-delay-induced distortion in conventional LC-ADC. Therefore, the resolution and power efficiency of the LC-ADC are improved effectively while maintaining the event-driven feature. Implemented in a 55nm process, the proposed LC-ADC achieves a scalable power consumption and a peak SNDR of 62.2dB for a 20kHz input. It also achieves a Walden FoM of 29.7fJ/conv.-step and a Schreier FoM of 158.6dB, which is best in class, without using off-chip calibration. Sub µW power is realized when the input frequency is below 1.5kHz. The proposed LC-ADC is also verified by simulated electrocardiogram (ECG), neural spike, and electromyogram (EMG) signals. It provides a ~7X data compression for ECG input, providing an attractive solution for time-sparse signal acquisition in biomedical applications.

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Succinate promotes pulmonary fibrosis through GPR91 and predicts death in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 µM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819-60.761)) and mortality (HR 3.418, 95% CI (1.308-8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis.

Discovery of N-Substituted Acetamide Derivatives as Promising P2Y14R Antagonists Using Molecular Hybridization Based on Crystallographic Overlay.

P2Y14 receptor (P2Y14R) is activated by uridine 5'-diphosphate-glucose, which is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2Y14R antagonists and the crystallographic overlap study between the reported P2Y14R antagonist compounds 6 and 9, a series of N-substituted-acetamide derivatives were designed, synthesized, and identified as novel and potent P2Y14R antagonists. The most potent antagonist, compound I-17 (N-(1H-benzo[d]imidazol-6-yl)-2-(4-bromophenoxy)acetamide, IC50 = 0.6 nM) without zwitterionic character, showed strong binding ability to P2Y14R, high selectivity, moderate oral bioactivity, and improved pharmacokinetic profiles. In vitro and in vivo evaluation demonstrated that compound I-17 had satisfactory inhibitory activity on the inflammatory response of monosodium urate (MSU)-induced acute gouty arthritis. I-17 decreased inflammatory factor release and cell pyroptosis through the NOD-like receptor family pyrin domain-containing 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway. Thus, compound I-17, with potent P2Y14R antagonistic activity, in vitro and in vivo efficacy, and favorable bioavailability (F = 75%), could be a promising lead compound for acute gouty arthritis.

Effects of different intrusion patterns during anterior teeth retraction using clear aligners in extraction cases: an iterative finite element analysis.

Background: Overtreatment design of clear aligner treatment (CAT) in extraction cases is currently primarily based on the clinical experience of orthodontists and is not supported by robust evidence on the underlying biomechanics. This study aimed to investigate the biomechanical effects of overtreatment strategies involving different maxillary anterior teeth intrusion patterns during anterior teeth retraction by CAT in extraction cases. Materials and methods: A finite element model of the maxillary dentition with the first premolar extracted was constructed. A loading method of clear aligners (CAs) based on the initial state field was proposed. The iterative method was used to simulate the long-term orthodontic tooth movement under the mechanical load exerted by the CAs. Three groups of CAs were utilized for anterior teeth retraction (G0: control group; G1: incisors intrusion group; G2: anterior teeth intrusion group). Tooth displacement and occlusal plane rotation tendency were analyzed. Results: In G0, CAT caused lingual tipping and extrusion of the incisors, distal tipping and extrusion of the canines, mesial tipping, and intrusion of the posterior teeth. In G1, the incisors showed minimal extrusion, whereas the canines showed increased extrusion and distal tipping tendency. G2 showed the smallest degree of posterior occlusal plane angle rotation, while the inclination tendency of the canines and second premolars decreased. Conclusion: 1. In CAT, tooth displacement tendency may change with increased wear time. 2. During anterior teeth retraction, the incisor intrusion pattern can provide effective vertical control for the lateral incisors but has little effect on the central incisors. Anterior teeth intrusion patterns can alleviate the inclination of canines and second premolars, resulting in partial relief of the roller-coaster effect.

Comparative transcriptome analysis of Fusarium graminearum challenged with distinct fungicides and functional analysis of FgICL gene.

Fusarium graminearum is an economically important phytopathogenic fungus. Chemical control remains the dominant approach to managing this plant pathogen. In the present study, we performed a comparative transcriptome analysis to understand the effects of four commercially used fungicides on F. graminearum. The results revealed a significant number of differentially expressed genes related to carbohydrate, amino acid, and lipid metabolism, particularly in the carbendazim and phenamacril groups. Central carbon pathways, including the TCA and glyoxylate cycles, were found to play crucial roles across all treatments except tebuconazole. Weighted gene co-expression network analysis reinforced the pivotal role of central carbon pathways based on identified hub genes. Additionally, critical candidates associated with ATP-binding cassette transporters, heat shock proteins, and chitin synthases were identified. The crucial functions of the isocitrate lyase in F. graminearum were also validated. Overall, the study provided comprehensive insights into the mechanisms of how F. graminearum responds to fungicide stress.

Influence of Zr Microalloying on the Microstructure and Room-/High-Temperature Mechanical Properties of an Al-Cu-Mn-Fe Alloy.

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al-Cu-Mn-Fe (ACMF) and Al-Cu-Mn-Fe-Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al2Cu and Al7Cu2Fe, and the Al2Cu phase dissolves into the matrix and re-precipitates as θ' phase during the T6 process. The introduction of Zr results in the precipitation of L12-Al3Zr nanometric precipitates after T6, while the θ' precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L12-Al3Zr precipitates were found coherently located with θ', which was assumed beneficial for stabilizing the θ' precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L12-Al3Zr, and θ' precipitates on the tensile properties were discussed. This work may be referred to for designing Al-Cu alloys for application in high-temperature fields.

Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production.

Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgGs production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgGs production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgGs production exhibited TIP (duration <60 days) and PIP (duration >368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were co-immunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgGs production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.

An Artificial Intelligence-Driven Approach for Automatic Evaluation of Right-to-Left Shunt Grades in Saline-Contrasted Transthoracic Echocardiography.

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.

Comparison of the outcomes of concurrent versus staged TAVR combined with PCI in patients with severe aortic stenosis and coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: The optimal timing for percutaneous coronary intervention (PCI) in patients undergoing transcatheter aortic valve replacement (TAVR) remains uncertain. This research aims to evaluate the results of patients diagnosed with severe aortic valve stenosis and coronary artery disease who undergo either simultaneous or staged PCI therapy during TAVR procedures. METHODS: We retrieved all relevant studies from our self-constructed databases up to January 2, 2024, encompassing databases such as Embase, Medline, Cochrane Library, and PubMed. RESULTS: A total of nine studies were included, and the results showed that both surgical modalities had good safety profiles in the early and long-term stages. For early endpoint events, the risk of all-cause mortality and major bleeding within 30 years was similar in the staged TAVR + PCI and the contemporaneous TAVR + PCI ( P > 0.05). Additionally, the risk of myocardial infarction, stroke, acute kidney injury and pacemaker implantation within 30 days or perioperatively is similar ( P > 0.05). For long-term endpoint events, the risk of all-cause mortality, myocardial infarction and stroke was similar in the two groups at ≥2 years ( P > 0.05). CONCLUSION: In patients undergoing TAVR who required coronary revascularization, no significant differences were observed in the early and long-term outcomes between those receiving concurrent TAVR and PCI versus staged surgery.

Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial.

BACKGROUND: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. METHODS: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. RESULTS: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. CONCLUSIONS: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04401800).

Genome-Wide Association Studies on Chinese Wheat Cultivars Reveal a Novel Fusarium Crown Rot Resistance Quantitative Trait Locus on Chromosome 3BL.

Fusarium crown rot (FCR), primarily caused by Fusarium pseudograminearum, has emerged as a new threat to wheat production and quality in North China. Genetic enhancement of wheat resistance to FCR remains the most effective approach for disease control. In this study, we phenotyped 435 Chinese wheat cultivars through FCR inoculation at the seedling stage in a greenhouse. Our findings revealed that only approximately 10.8% of the wheat germplasms displayed moderate or high resistance to FCR. A genome-wide association study (GWAS) using high-density 660K SNP led to the discovery of a novel quantitative trait locus on the long arm of chromosome 3B, designated as Qfcr.hebau-3BL. A total of 12 significantly associated SNPs were closely clustered within a 1.05 Mb physical interval. SNP-based molecular markers were developed to facilitate the practical application of Qfcr.hebau-3BL. Among the five candidate FCR resistance genes within the Qfcr.hebau-3BL, we focused on TraesCS3B02G307700, which encodes a protein kinase, due to its expression pattern. Functional validation revealed two transcripts, TaSTK1.1 and TaSTK1.2, with opposing roles in plant resistance to fungal disease. These findings provide insights into the genetic basis of FCR resistance in wheat and offer valuable resources for breeding resistant varieties.

Uncovering the photosystem I assembly pathway in land plants.

Photosystem I (PSI) is one of two large pigment-protein complexes responsible for converting solar energy into chemical energy in all oxygenic photosynthetic organisms. The PSI supercomplex consists of the PSI core complex and peripheral light-harvesting complex I (LHCI) in eukaryotic photosynthetic organisms. However, how the PSI complex assembles in land plants is unknown. Here we describe PHOTOSYSTEM I BIOGENESIS FACTOR 8 (PBF8), a thylakoid-anchored protein in Arabidopsis thaliana that is required for PSI assembly. PBF8 regulates two key consecutive steps in this process, the building of two assembly intermediates comprising eight or nine subunits, by interacting with PSI core subunits. We identified putative PBF8 orthologues in charophytic algae and land plants but not in Cyanobacteria or Chlorophyta. Our data reveal the major PSI assembly pathway in land plants. Our findings suggest that novel assembly mechanisms evolved during plant terrestrialization to regulate PSI assembly, perhaps as a means to cope with terrestrial environments.

Small extracellular vesicles derived from acute myeloid leukemia cells promote leukemogenesis by transferring miR-221-3p.

Small extracellular vesicles (sEVs) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNAs (miRNAs) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cells-derived sEVs (AML-sEVs) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEVs. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEVs impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEVs-delivered miRNAs contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.

Maresin-1 Attenuates Sepsis-Associated Acute Kidney Injury via Suppressing Inflammation, Endoplasmic Reticulum Stress and Pyroptosis by Activating the AMPK/SIRT3 Pathway.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation. Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay. Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1ß and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1ß also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1's protective effects in septic mice. Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.